In this meta-analysis, we conducted a rigorous search of all available published cohort studies to quantify the possible association between insulin use and incidental DR in individuals with type 2 diabetes. Although a dramatic heterogeneity existed in this study, the significant association between insulin use and DR was detected. The subgroup analyses by study design, region, data source and adjustment of HbA1c yielded similar results. In the group when the DM duration was adjusted, no significant result was reported.
Insulin and DR risk have been discussed for long. Several cross-sectional studies have reported that insulin use is a risk factor for DR. In certain cross-sectional studies, the association between insulin use and risk of DR was reported [15, 16]. According to data from the Tromsø Eye Study, a study including 514 participants with diabetes aged from 46 to 87 years, showed that DR risk was associated with insulin use (OR 2.14, 95% CI 1.19-3.85) . In another cross-sectional study performed among 261 type 2 diabetic patients at Chandrubeksa Hospital on January 2011, the result demonstrated that the patients who had received insulin treatment were more likely to suffer from DR than those who had not (OR 3.95, 95% CI 1.86, 8.39) . However, considering that various potential sources would be involved in cross-sectional study design, a cohort study design would be preferred for yielding less potential bias. Meta-analysis is now a useful statistical tool to pool relevant studies together and gain a more powerful conclusion. The meta-analysis was also used in the search for potential risk factors for DR. Zhang et al. reported that in a meta-analysis including nine studies with 1, 217 cases and 1, 459 controls, 4G/5G polymorphism in the PAI-1 gene potentially increased the risk of DR in type 2 diabetes and showed a discrepancy between different ethnicities . In this study, we conducted a meta-analysis only including cohort studies to investigate the association between insulin use and risk of DR. The high methodological quality of included studies and powerful statistical tool employed in this meta-analysis combinely supported the reliability of the presented robust conclusion.
In the subgroup analyses, we found that the association between insulin use and DR risk became non-significant when the DM duration was adjusted. It suggested that the increasing risk of DR in insulin users might be associated with a longer DM duration, while DM duration was generally accepted as a risk factor for DM [19, 20]. In the subgroup analyses by other confounding factors, no different results were found. The underlying mechanism of the association between insulin use and risk of DR should be further explored in more studies. In our meta-analysis with seven cohort studies included, we pointed that insulin use might be a risk factor of DR. This finding pointed that we should be more discreet in the patients with long time insulin use history and the DR detection should be more careful. Besides, as insulin use is reported to be risk factor of different diseases [21, 22], any inapposite insulin use in the treatment of patients should be avoided.
Only cohort studies were enrolled in the present meta-analysis, which helps to add strength to our study. Besides, access to adequate literature and detailed analyses of the outcome also provide us with detailed understanding of the correlation between insulin use and DR risk. However, limitations of this meta-analysis should also be noted. First, among all the included studies, not enough studies provided the data of insulin use and NPDR or PDR risk, which make it difficult to further explore the role of insulin take in DR onset and progression. Second, considering that only seven cohort studies were included, the power of the conclusion was relatively limited. The third limitation is that most studies lack a long enough follow-up duration and thus more studies are needed to confirm our conclusion.